The indole-indoline alkaloids, the most important of which can be represented by the compound of formula I ##STR1## wherein R.sub.2 is acetoxy or hydroxy; and R is formyl or methyl include vinblastine and vincristine, which are anti-tumor agents widely used in the treatment of cancer. These agents have been prepared from extracts of the Vinca rosea plant. As these alkaloids are present in the plant only in very small concentrations and since they must be separated from many other companion alkaloids, their synthetic generation becomes particularly valuable.
Preparation of compounds of formula I, by a pathway quite different from that of the present invention, has already been described. Thus Potier and Kutney obtained products with the C18'S-C2'R absolute configuration, which is critical for anti-tumor activity, by a coupling reaction of the N.sup.b -oxide of catharanthine, or its derivatives, with vindoline, in the presence of trifluoroacetic anhydride, followed by a reduction reaction. [See Potier et al J. Am. Chem. Soc. 98, 7017 (1976) and Kutney et al Helv. Chim. Acta, 59, 2858 (1976)].
The Potier and Kutney coupling process has disadvantages. The yields are not satisfactory except for the coupling of catharanthine N-oxide with vindoline and even there the preparative yield is low. While vindoline is the most abundant alkaloid of Vinca rosea and is thus readily available, the other possible components of the Potier-Kutney coupling process (catharanthine, allocatharanthine, voacangine,) are relatively inaccessible, costly, and they do not allow a wide range of structural variation of that component of the coupling process.